SUMMARY
Bladder cancer is the 10th-most frequently detected cancer in both sexes and 9th-most lethal malignancy in men. Invasive bladder cancer has a high inci¬dence of recurrence, which contributes to the high mortality of this disease. In Egypt, carcinoma of the bladder is the most prevalent cancer, accounting for as many as 31% of all cancer cases.
The global burden of bladder cancer is predicted to increase significantly in the foreseeable future as a result of the progression of the tobacco epidemic and increasing exposure to occupational carcinogens in developing countries.
Currently, the combination of cystoscopy and urine cytology is the gold standard for diagnosis of bladder tumors. Therefore, there is an urgent need for cost-efficient, highly specific, and sensitive non-invasive markers as an alternative for bladder cancer diagnosis, screening, and follow-up. While numerous urinary tests have been developed and several were FDA-approved, none of them has been implemented in clinical routine for diagnosis or follow-up of BCa.
NDRG-2 is a candidate tumor suppressor gene, and several studies have confirmed that it plays an important role in cell proliferation, apoptosis and metastasis.
IGF-2 is a potent tissue growth factor which plays a fundamental role in the epithelial– mesenchymal transition (EMT) process. The over expression of IGF2 has been identified in many forms of human cancer.
The study involved 70 subjects of both sexes. Their ages ranged from 30-84 years. They were categorized into 2 groups:
I- Bladder cancer group: included 50 patients with histopathologically diagnosed primary or recurrent bladder carcinoma.
II- Control group: included 20 persons with histopathologically normal urothelium.
A single and naturally voided midstream urine sample will be obtained before cystoscopy and tissue biopsy. Tissue biopsy will be obtained during endoscopic removal of renal or ureteric stones for control group.
All patients were subjected to:
1. Full history taking.
2. General and local urological examinations.
3. Routine preoperative laboratory investigations including: urine analysis, complete blood count (CBC), fasting blood sugar, liver function tests, kidney function tests and coagulation profile.
4. Radiological investigations including: abdominopelvic plain X-ray, ultrasonography, and CT.
5. ECG (if indicated for preoperative assessment).
6. Diagnostic cystoscopy and biopsy for histopathology.
7. Voided urine cytology specimens will be prepared from all urine specimens.
8. Molecular biology investigations: Quantitative reverse transcription polymerase chain reaction (qRT-PCR) for detection of NDRG-2 and IGF-2 urinary expression levels.
The results of the present study showed that urinary genetic expression of NDRG-2 was significantly decreased in bladder cancer patients as compared to control group with significant difference among the cancer group as regard the tumor stage and grade.
Whereas the urinary genetic expression of IGF-2 was significantly increased in bladder cancer patients as compared to control group with significant difference among the cancer group as regard the tumor stage and grade.
Moreover, there was a significant negative correlation between NDRG-2 urinary expression level and tumor grade, while IGF-2 urinary expression level was positively correlated with tumor grade.
NDRG-2 was found to be the most sensitive in diagnosis of bladder cancer with sensitivity and specificity were 100% and 98% respectively. On the other hand, the sensitivity and specificity of IGF-2 were 78.0% and 60.0% respectively. In our study, the sensitivity of VUC was 67.4% and 100% specificity.
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